DIFFERENTIAL-EFFECTS OF PLATELET-DERIVED GROWTH-FACTOR ISOFORMS ON PLASMINOGEN-ACTIVATOR ACTIVITY IN FETAL-RAT OSTEOBLASTS DUE TO ISOFORM-SPECIFIC RECEPTOR FUNCTIONS

We examined receptor binding and metabolic effects of the platelet-der ived growth factor (PDGF) isoforms AA, AB, and BB in cultures of osteo blastic cells from fetal rat calvaria. Saturation binding experiments demonstrated the presence of 6,000 binding sites for PDGF-AA, 42,000 f or PDGF-AB, and 60,000 for PDGF-BB. Binding competition experiments we re compatible with the recently postulated model of three PDGF recepto r subtypes with differential affinity for the PDGF isoforms. The effec ts of the PDGF isoforms on DNA synthesis, collagen synthesis, and alka line phosphatase activity in osteoblasts strictly correlated with the number of available binding sites. Accordingly, PDGF-BB was the most p otent isoform, PDGF-AB was slightly less potent, and PDGF-AA was the l east potent. In contrast, we found that PDGF-BB was less potent than P DGF-AB in increasing plasminogen activator activity in the osteoblast- conditioned medium. Our data strongly suggest that the PDGF receptor s ubtypes in fetal rat osteoblasts not only selectively bind one or more PDGF isoforms, but are also capable of responding differently to thes e isoforms.